Significance Modern anesthetic practice has been replacing the use of volatile agents to intravenous anesthetic drugs for the maintenance of anesthesia for major surgical procedures. Fentanyl is routinely used to reduce the requirement of other anesthetic drugs described as the MAC reduction effect. Objectives This study was designed to investigate the effect of three intravenous infusion doses of fentanyl (FEN) in rhesus monkeys. Following instrumentation and baseline, ISO MAC was determined in triplicate for each animal. Each animal then received each of three infusions of fentanyl 0.132 (g/kg/min, 0.264 (g/kg/min and 0.396 (g/kg/min in increasing dose. A loading dose of 1.5 (g/kg fentanyl preceded each infusion. Each infusion was maintained for 30 minutes before initiating MAC determination. Plasma fentanyl samples were obtained prior to the administration of the FEN loading dose at each infusion level at 30 minutes from the start of each FEN infusion and mid-way through MAC determination at each infusion. Results The baseline ISO MAC was 1.53 1 0.7%. Isoflurane MAC decreased -19 1 5.0%, - 44 1 8.9% and - 59.8 1 6.8% with fentanyl doses of 0.132 (g/kg/min, 0.264 (g/kg/min and 0.396 (g/kg/min, respectively. Corresponding fentanyl plasma concentrations were 3.14 1 0.67 ng/ml, 6.7 1 0.43 ng/ml and 12.78 1 1.23 ng/ml, respectively. Temperature and blood gas data do not appear to change significantly over time or between dose groups. The results indicate that in rhesus monkeys, ISO MAC is reduced by FEN, and that there is a close relationship between the concentration of FEN in plasma and its isoflurane sparing effect. Future Directions Research of other anesthetic protocol with the use of propofol. KEYWORDS anesthesia, opioid, fentanyl, MAC